TORCH-R trial protocol: hypofractionated radiotherapy combined with chemotherapy and toripalimab for locally recurrent rectal cancer: a prospective, single-arm, two-cohort, phase II trial

Juefeng Wan; Ruiyan Wu; Miaomiao Fu; Lijun Shen; Hui Zhang; Yan Wang; Yaqi Wang; Shujuan Zhou; Yajie Chen; Fan Xia; Zhen Zhang

doi:10.3389/fonc.2023.1304767

TORCH-R trial protocol: hypofractionated radiotherapy combined with chemotherapy and toripalimab for locally recurrent rectal cancer: a prospective, single-arm, two-cohort, phase II trial

Front Oncol. 2023 Nov 20:13:1304767. doi: 10.3389/fonc.2023.1304767. eCollection 2023.

Authors

Juefeng Wan^#^{1

2

3}, Ruiyan Wu^#^{1

2

3}, Miaomiao Fu^#^{1

2

3}, Lijun Shen^{1

2

3}, Hui Zhang^{1

2

3}, Yan Wang^{1

2

3}, Yaqi Wang^{1

2

3}, Shujuan Zhou^{1

2

3}, Yajie Chen^{1

2

3}, Fan Xia^{1

2

3}, Zhen Zhang^{1

2

3}

Affiliations

¹ Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
² Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
³ Shanghai Clinical Research Center for Radiation Oncology, Shanghai Key Laboratory of Radiation Oncology, Shanghai, China.

^# Contributed equally.

Abstract

For patients with locally recurrent rectal cancer (LRRC), the response rate to chemoradiotherapy is 40%-50%. Additionally, only approximately 40%-50% of patients with recurrent rectal cancer are able to undergo R0 resection. Recent studies in locally advanced rectal cancer (LARC) have shown promising synergistic effects when combining immunotherapy (PD-1/PD-L1 antibodies) with neoadjuvant chemoradiotherapy (nCRT). Therefore, incorporating immunotherapy into the treatment regimen for LRRC patients has the potential to further improve response rates and prognosis. To investigate this, the TORCH-R trial was conducted. This prospective, single-arm, two-cohort, phase II trial focuses on the use of hypofractionated radiotherapy, chemotherapy, and immunotherapy in LRRC patients without or with oligometastases. The trial will include two cohorts: cohort A consists of rectal cancer patients who are treatment-naive for local recurrence, and cohort B includes patients with progressive disease after first-line chemotherapy. Cohort A and cohort B patients will receive 25-40 Gy/5 Fx irradiation or 15-30 Gy/5 Fx reirradiation for pelvic recurrence, respectively. Subsequently, they will undergo 18 weeks of chemotherapy, toripalimab, and stereotactic ablative radiotherapy (SABR) for all metastatic lesions between chemoimmunotherapy cycles. Decisions regarding follow-up of complete response (CR), radical surgery, sustained treatment of non-resection, or exiting the trial are made by a multidisciplinary team (MDT). The primary endpoint of this study is the local objective response rate (ORR). The secondary endpoints include the extrapelvic response rate, duration of response, local recurrence R0 resection rate, progression-free survival (PFS), overall survival (OS), and safety and tolerability. Notably, this trial represents the first clinical exploration of inducing hypofractionated radiotherapy, chemotherapy, and immunotherapy in LRRC patients.

Clinical trial registration: https://clinicaltrials.gov/study/NCT05628038, identifier NCT05628038.

Keywords: SAbR; chemotherapy; hypofractionated radiotherapy; immunotherapy; locally recurrent rectal cancer.

Associated data

ClinicalTrials.gov/NCT05628038

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by TopAlliance IIT Funding (grant number JS001-ISS-CO401). The founder did not have any role in the design of the study and will not have any role in the collection, analysis, and interpretation of data or in writing the manuscript. This study was also supported by the National Key R&D Program of China (2022YFC2503700 and 2022YFC2503702), the National Natural Science Foundation of China (82002905 and 82003229), the Shanghai Sailing Plan (20YF1408300), and the Key Clinical Specialty Project of Shanghai.